This research focuses on the molecular and biochemical origins of sunlight-induced skin cancers in man. It addresses three aspects of the problem: (1) sunlight-induced damage to DNA, (2) cellular enzymes for repair of such damage and (3) consequences of failure of repair. These problems are studied in four experimental approaches: first, delineation of the kinds, number and distribution of DNA lesions induced in human skin irradiated in situ, in neonatal human foreskins and in isolated DNA by irradiation with radiation in the wavelength range of 220-400 nm; second, determination of the paths and rates of repair of such DNA lesions in skin irradiated in situ; third, study of the activity and structure of DNA repair enzymes, in specific, DNA photoreactivating enzymes from man and E. coli; and fourth, determination of the molecular changes in DNA of sunlight-induced skin cancers using a human cell DNA transfection system developed in this laboratory. These studies should give insights into solar oncogenesis in man, from introduction of the initial lesion, cellular repair and/or failure of repair, and molecular changes in DNA in human skin cancers.